Gene expression profiles in human malignant melanoma cell lines exposed to carbon ions or X-rays

Little is known about molecular mechanism for its effectiveness of C-ions in melanomas. In this study, we examined the cytotoxic effects of C-ions on 6 human malignant melanoma cell lines, and gene expression profiles and cell cycle progression were also examined to reveal the mechanism of the therapeutic effectiveness of C-ions. Equivalent doses of the C-ions were more effective at reducing the survival rates than X-rays, and the relative biological effectiveness (RBE) was > 2.0 in all cell lines. In unsupervised 2D clustering performed for C-ions irradiated groups at 1 h after irradiation, many of the probes were down-regulated among 6 cell lines. We identified probes, such as XKRY, ELA3A, T-STAR, SCN9A, ELA2A, CRK7, CCNA2, CROP, CYR61, SDFR1, and SMAD4 differentially responded to C-ions and X-rays among 4 cell lines. CCNA2 was down-regulated by C-ions more than X-rays at 3 h after irradiation, and C-ions induced G2/M arrest more than X-rays in three cell lines at 30 h. Many of p53 target genes, such as ATF3, BTG2, CDKN1A, GADD45A, SESN1, and TNFRSF6 were up-regulated by C-ions at 3 h. The expressions of p53 target genes were not changed in HMV-I and MeWo. In MeWo, APG3L, RPL26 and PCNA were down-regulated or E2F2 and LIMS3 were up-regulated, and in HMV-I, ATF3, FOS, and CYR61 were up-regulated at 1 h after C-ions. In conclusion, C-ions affected p53-dependent and p53-independent pathways of cell death and cell cycle. Individual mechanism in activating of cell death was observed in each cell line of 6 melanomas. Keywords: Specific gene expression prfiles after carbon ion irradiation To study the gene expression profiles in human melanoma cell lines exposed to carbon ions or X-rays. We used 6 cell lines, 92-1, C32TG, Colo679, HMV-I, HMV-II, and MeWo. Cells were irradiated with 2Gy of carbon ions or X-rays, and total RNA was extracted. We used human whole genome array (55k).